Day: November 4, 2015

Spinal cord injuries represent an immensely difficult problem for regenerative medicine. The extensive nature of the damage to the spinal cord is difficult to repair, and the transformation that the injury wrecks in the spinal cord makes the spinal cord inhospitable to cellular repair.

Fortunately some headway is being made, and several clinical trials have shown some success with particular stem cells. Neural stem cells can differentiate into new neurons and glial cells and replace dead or damaged cells (see Tsukamoto A., et Al., Stem Cell Res Ther4,102, 2013 ). Oligodendrocyte progenitor cells (OPCs) derived from embryonic stem cells or other sources can replace the myelin sheath that died off as a result of the injury (Alsanie WF, Niclis JC, Petratos S. Stem Cells Dev. 2013 Sep 15;22(18):2459-76). Olfactory ensheathing cells can move across the glial scar and facilitate the regrowth of severed axons across the scar (Tabakow P, et al., Cell Transplant. 2014;23(12):1631-55). Mesenchymal stem cells can mitigate the inflammation in the damaged spinal cord, and, maybe, stimulate endogenous stem cell populations to repair the spinal cord (Geffner L.F., et al., Cell Transplant17,1277, 2008). Therefore, several cell types seem to have some ability to heal the damaged spinal cord.

A new clinical trial from the Zali laboratory at Shahid Beheshti University of Medical Sciences, in Tehran, Iran, has examined the used of two different stem cells to treat spinal cord injury patients. This trial was a small, Phase I trial that only tested the safety of these treatments.

Zali and his colleagues assessed the safety and feasibility of transplanting a combination of bone marrow mesenchymal stem cells (MSCs) and Schwann cells (SCs) into the cerebral spinal fluid (CSF) of patients with chronic spinal cord injury. SCs are cells that insulate peripheral nerves with a myelin sheath. Even though SCs are not found in the central nervous system, they do the same job as oligodendrocytes, and several experiments have shown that when transplanted into the central nervous system, SCs can do the job of oligodendrocytes in the central nervous system.

In this trial, six subjects with complete spinal cord injury according to International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI) developed by the American Spinal Injury Association were treated with co-transplantation of their own MSCs and SCs by means of a lumbar puncture. The neurological status of these patients was ascertained by the ISNCSCI and by assessment of each patient’s functional status according to the Spinal Cord Independent Measure. Before and after cell transplantation, the spinal cord of each patient was imaged by means of magnetic resonance imaging (MRI). All patients also underwent electromyography, urodynamic study (UDS) and MRI tractograghy before the procedure and after the procedure if patients reported any changes in motor function or any changes in urinary sensation.

In a span of 30 months following the procedure, radiological findings were unchanged for each patients. There were no signs or indications of neoplastic tissue overgrowth in any patient. In one patients, their American Spinal Injury Association class was downgraded from A to B. This same patients had increased bladder compliance, which correlated quite well with the axonal regeneration detected in MRI tractography. None of these patients showed any improvement in motor function.

To summarize, there were no adverse effects detected around 30 months after the transplantations. These results suggest that this stem cell combination is safe as a treatment for spinal cord injury. While improvement of observed in one patients, because the trial was not designed to investigate the efficacy of the treatment, it is difficult to make any hard-and-fast conclusions about the efficacy of this treatment at this time. However, the fact that one patient did improve is at least encouraging.